Side Effects News & Reports

Attorney Tom Lamb started practicing law in 1988. He has been representing patients and their families in drug injury lawsuits as his primary practice area for the past 18 years. For more legal and medical information about drug side effects cases, visit our website: DrugInjuryLaw.com

Please refer to your Supplemental New Drug Application (sNDA) dated and received June 23, 2017....

This Prior Approval supplemental new drug application provides for a new subsection under the Warnings and Precautions section entitled Pathological Gambling and Other Compulsive Behaviors and corollary revisions to the Highlights, Adverse Reactions, Patient Counseling Information, and Medication Guide.

Post-marketing case reports suggest that patients can experience intense urges, particularly for gambling, and the inability to control these urges while taking REXULTI. Other compulsive urges, reported less frequently, include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or intense gambling urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or other urges while being treated with REXULTI. In some cases, although not all, urges were reported to have stopped when the dose was reduced or the medication was discontinued. Compulsive behaviors may result in harm to the patient and others if not recognized. Consider dose reduction or stopping the medication if a patient develops such urges.

The drug companies responsible for Rexulti in the US are Otsuka Pharmaceutical Co., Ltd. (Japan), Otsuka America Pharmaceutical, Inc. (Maryland), and Lundbeck (Illinois).

Our law firm is investigating possible products liability lawsuits against those companies for people who have experienced compulsive gambling behaviors while using Rexulti. Those cases would involve one or more of the following consequences: personal debt; bankruptcy; home foreclosure; divorce; unemployment; emotional trauma; and, damaged reputation.

If we can be of assistance to you or a loved one as regards a possible Rexulti drug injury legal compensation case, please do not hesitate to contact us.

Label Changes Announced By FDA In December 2017 Finally Approved For Magnevist, Omniscan, And Other GBCAs In April 2018

Gadolinium based contrast agents (GBCAs) are substances that are injected into patients during a Magnetic Resonance Imaging (MRI) or Magnetic Resonance Angiography (MRA) in order to produce clearer radiology images.

Over the past couple of years drug regulators around the world have started to pay attention to so-called "side effect" of certain GBCAs called Gadolinium Deposition Disease (GDD), which is a form of gadolinium toxicity and sometimes called, instead, Gadolinium Storage Condition.

In comparison, at the present time FDA is only requiring that there be certain changes made to the Prescribing Information, or drug label, of all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) in the US. To be clear, none of these products will be recalled from the market here.

Gadolinium is retained for months or years in several organs. The highest concentrations (nanomoles per gram of tissue) have been identified in the bone, followed by other organs (e.g. brain, skin, kidney, liver, and spleen). The duration of retention also varies by tissue and is longest in bone. Linear GBCAs cause more retention than macrocyclic GBCAs. At equivalent doses, gadolinium retention varies among the linear agents with Omniscan (gadodiamide) and Optimark (gadoversetamide) causing greater retention than other linear agents [Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), MultiHance (gadobenate dimeglumine)]. Retention is lowest and similar among the macrocyclic GBCAs [Dotarem (gadoterate meglumine), Gadavist (gadobutrol), ProHance (gadoteridol)].

It is important to understand that symptoms of gadolinium-related medical conditions can first appear anywhere from just a few hours until several weeks after the MRI or MRA procedure when a GBCA dye was administered by injection.

Some of the more common symptoms reported by patients are:

Severe pain in the bones, joints, arms, and legs

Sensation of sharp pins and needles, cutting, or burning

Thickening of soft-tissue, tendons, and ligaments

Tightness in the hands and feet

Nausea / vomiting

Cognitive impairment

Clouded mentation (“brain fog”)

Persistent headache

Our law firm is investigating possible products liability lawsuits against the pharmaceutical companies responsible for the gadolinium-based contrast agents, or contrast dyes, which might cause any of these symptoms.

Gadolinium Deposition Disease Symptoms Typically Begin Couple Of Months After Use And Can Continue For Many Years Without Any Diagnosis

During MRI and MRA procedures patients often receive injections of gadolinium-based contrast agents (GBCAs). Some of those contrast agents with gadolinium are classified as linear GBCAs -- as opposed to macrocyclic gadolinium contrast agents.

Some of the more popular linear contrast agents are Magnevist, Omniscan, and Multihance. The Radiology Report medical record document for an MRI or MRA "with contrast" usually shows the brand name of the GBCA injected for the procedure.

A person who received an injection of Magnevist, for example, may develop some symptoms in the couple of months following their MRI or MRA procedure. These various gadolinium-related symptoms include:

Persistent headache;

"Brain fog";

Skin that appears spongy or rubbery, which is actually subcutaneous soft tissue thickening;

Tendons and ligaments which are painful and have a thickened appearance;

Bone and joint pain;

Tightness in hands and feet; and,

Pain described as burning, cutting, or "pins and needles" in the arms or legs and the torso.

If a person starts experiencing one or more of these symptoms within two months after a linear gadolinium contrast agent was used, they may have developed gadolinium toxicity or poisoning due to the GBCA injection they received for their MRI. This serious medical condition was rarely recognized in the medical community until the past couple of years, when it has begun to be diagnosed and labelled as "gadolinium deposition disease".

Where gadolinium toxicity is suspected by a patient or a doctor, testing for retained gadolinium is the next step in determining whether the symptoms are, in fact, due to the gadolinium contrast agent used for the MRI or MRA. There are two types of tests which might be used:

24-hour urine gadolinium test; and

Heavy metal testing using blood, hair or nail samples, or urine.

If one or both of these tests are "positive" for gadolinium, the symptoms experienced by that person may be diagnosed by a doctor as related to the contrast agent injected before their MRI or MRA.

For background we direct you to this medical journal article, "Gadolinium in Humans: A Family of Disorders", by Richard C. Semelka, MD, et al., published in the August 2016 edition of American Journal of Roentgenology.

In large part, as seen in the two excerpts set forth which follow, it is this 2016 medical article by Dr. Semelka that raised the profile of this relatively new set of side effects associated with gadolinium-based contrast agents (GBCAs).

We begin with a diagnostic label suggested by Dr. Semelka for the constellation of symptoms that are listed above:

“Gadolinium deposition disease” is the name we propose for a disease process observed in subjects with normal or near normal renal function who develop persistent symptoms that arise hours to 2 months after the administration of [gadolinium-based contrast agents (GBCAs)]. In these cases, no preexistent disease or subsequently developed disease of an alternate known process is present to account for the symptoms.

Then we take a closer look at those various symptoms:

In our experience, symptoms of gadolinium deposition disease are similar but not identical to those observed in [nephrogenic systemic fibrosis (NSF)]. Typical clinical features include persistent headache and bone and joint pain. Patients often complain of clouded mentation that many describe as a “brain fog.” More distinctive features are comparable with those observed in NSF but of lesser severity; patients often experience subcutaneous soft-tissue thickening that clinically appears somewhat spongy or rubbery without the hardness and redness observed in NSF. Tendons and ligaments in a comparable distribution may also be painful and have a thickened appearance. Patients may complain of tightness of the hands and feet that resembles the feeling of being fitted with extremely tight gloves or socks. Patients may experience excruciating pain, typically in a distal distribution, of the arms and legs but that may also be in the torso or generalized in location. This pain is often described as feeling like sharp pins and needles, cutting, or burning.

For more about this still-developing drug injury situation, you might want to visit our Gadolinium Based Contrast Agents Side Effects information page. As indicated there, our law firm is investigating possible products liability lawsuits against the pharmaceutical companies responsible for the linear gadolinium-based contrast agents, or contrast dyes, which might cause any of the several symptoms that fall under the gadolinium deposition disease diagnosis label.

Onglyza, Nesina, Januvia, and Tradjenta Are Included In This Popular Class Of Type-2 Diabetes Medications

In April 2016 the FDA took regulatory action by mandating label changes with new warnings about an increased risk of heart failure for these relatively new diabetes medicines in the dipeptidyl peptidase-4 (DPP-4) inhibitor drug class:

Onglyza (saxagliptin)

Kombiglyze XR (saxagliptin and metformin)

Nesina (alogliptin)

Kazano (alogliptin and metformin)

Oseni (alogliptin and pioglitazone)

Qtern (dapagliflozin and saxagliptin)

In connection with that DPP-4 diabetes drug label change as well as related earlier FDA actions, some medical researchers recently took a look at heart-related side effects reports submitted to FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.

From the Abstract for a subsequent medial journal article with their findings, in the Conclusions section:

Postmarketing surveillance of DPP‐4i through FAERS suggest increased reporting of [major adverse cardiac events (MACE)], supporting the current FDA warning of heart failure risk. This suggests the need for additional longitudinal, observational research into the association of [dipeptidyl peptidase‐4 inhibitors (DPP‐4i)] and other [major adverse cardiac events (MACE)].

Comparing these recent findings to the increased drug label warnings about heart failure which were mandated by the FDA for certain DPP-4 diabetes drugs back in 2016:

It seems that Tradjenta and Jentadueto could have had similar increased warnings for heart failure added in April 2016 rather than in August 2017 -- and this type of label change for Glyxambi was not made until December 2017;

It is suggested that Nesina, Kazano, and Oseni should have stronger warnings for myocardial infarction (MI), more commonly referred to as heart attack; and,

It is suggested that Januvia, Janumet, and Janumet XR should have stronger warnings for cerebral infarction, more generally known as cerebrovascular accident (CVA) or stroke.

We would be interested in reviewing events of heart failure, myocardial infarction, and cerebral infarction for patients who used any of the DPP-4 diabetes drugs -- like Onlgyza, Nesina, Januvia, and Tradjenta -- as possible drug injury lawsuits against the responsible drug companies. (Get a Free Diabetes Drugs Case Evaluation)

Of course, we will continue to monitor the safety profile for all the DPP-4 diabetes drugs and watch for future possible FDA regulatory actions, such as drug label changes with stronger warnings about heart attacks and/or strokes.

This Relatively New Parkinson's Disease Drug Already Been Implicated In Hundreds Of Death Cases, While Only Being On Market Since 2016

Two years ago the FDA approved Nuplazid (pimaveanserin) as a new kind of antipsychotic drug which is intended to treat hallucinations, delusions, and other symptoms of psychosis among patients with Parkinson’s disease. Reportedly, for this particular medical condition there is a patient population numbering in the hundreds of thousands with a typical onset around age 65.

An FDA Advisory Committee considered whether to recommend approval of Nuplazid in March 2016. In more detail, according to the April 2018 CNN Investigates story:

The committee voted 12-2 and recommended that the FDA approve Nuplazid for the treatment of Parkinson's disease psychosis based on a six-week study of about 200 patients. Three previous studies of the drug did not show that it was effective, [the physician who led the FDA's medical review, Dr. Paul Andreason] said in his medical review, though they showed similar risk.

Even some committee members who voted in favor of the drug expressed reservations, according to the hearing transcript. "I guess I'm hoping that the risks are going to be small, and I think the benefits for some of these people who are very sick and whose families are affected by this, I think they're probably willing to take that risk," one physician stated. Another committee member said she wouldn't have voted for the drug's approval if there had been a safe and effective alternative on the market. A third made a "plea" to the FDA to "consider a large observational study so we can ensure that, once it goes into real-world use, that the benefits will outweigh the risks."

Nuplazid was thereafter approved by the FDA in April 2016, and became available to US patients in June 2016.

Shortly after the drug's release, patients' family members, doctors and other health care professionals started reporting "adverse events" possibly linked to the medication -- including deaths, life-threatening incidents, falls, insomnia, nausea and fatigue. In more than 1,000 reports, patients continued to experience hallucinations while on Nuplazid.

In November, an analysis released by a nonprofit health care organization, the Institute for Safe Medication Practices, warned that 244 deaths had been reported to the FDA between the drug's launch and March 2017. The organization also noted that hundreds of reports suggested the drug was "not providing the expected benefit" or potentially worsening the condition....

Since the institute released its analysis, FDA data shows that the number of reported deaths has risen to more than 700. As of last June, Nuplazid was the only medication listed as "suspect" in at least 500 of the death reports.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson's disease psychosis [see Warnings and Precautions 5.1)].

Nonetheless, Nuplazid is drawing increased scrutiny, as demonstrated by these two excerpts from the April 2018 CNN news story which focuses on patient deaths:

"This is almost unheard of, to have this many deaths reported," said Diana Zuckerman, founder and president of the nonprofit thinktank the National Center for Health Research, adding that because reports are voluntary, potential problems may be underreported. "You just don't see this with most new drugs -- you don't see all these reports -- so you have to take it seriously."

Geriatric psychiatrist and former FDA medical officer Susan Molchan said that the number of deaths is alarming and questioned whether patients and their families are aware of the risks associated with the drug.

We will continue to watch developments concerning the safety profile of Nuplazid, including possible regulatory action by the FDA.

New Study Finds Overall 75% Increase In Risk Of IBD, And Association Peaked Between 3 And 4 Years Of Use

According to an observational study published on March 21, 2018 by The BMJ -- formerly known as British Medical Journal -- the use of dipeptidyl peptidase-4 (DPP-4) inhibitors for treatment of type 2 diabetes is associated with increased risk for inflammatory bowel disease (IBD).

The following diabetes medicines are in the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs:

To our knowledge, this is the first observational study to specifically investigate the association between the use of dipeptidyl peptidase-4 inhibitors and the incidence of inflammatory bowel disease. Use of dipeptidyl peptidase-4 inhibitors was associated with an overall 75% increase in risk of inflammatory bowel disease. In secondary analyses, the association was particularly elevated between three and four years of use and between two and four years after the start of dipeptidyl peptidase-4 inhibitor treatment. This gradual increase in the risk is consistent with the hypothesis of a possible delayed effect of the use of dipeptidyl peptidase-4 inhibitors on the incidence of inflammatory bowel disease. This association remained highly consistent across a variety of sensitivity analyses.

Later in the same part of that March 2018 BMJ medical journal article, we get these details:

Finally, our results indicate that an increased risk with dipeptidyl peptidase-4 inhibitors may be associated with ulcerative colitis and not Crohn’s disease. However, this finding should be interpreted with caution as this stratified analysis was based on few events, generating a wide confidence interval with an upper 95% confidence limit of 2.09. Thus, our results do not rule out a possible association with Crohn’s disease as well. In summary, although our findings need to be replicated, additional studies are also needed to understand the possible mechanism through which dipeptidyl peptidase-4 inhibitors may increase the risk of inflammatory bowel disease.

As background, we point out that this is not the first time there have been safety concerns about the dipeptidyl peptidase-4 (DPP-4) inhibitors:

In April 2016 the FDA took regulatory action by mandating label changes with new warnings about an increased risk of heart failure for some of these DPP-4 inhibitor diabetes medicines, including Onglyza and Kombiglyze.

In March 2016 the FDA said it was evaluating the need for possible regulatory action as regards all of the DPP-4 diabetes drugs due to the side effects of renal failure or kidney failure.

In August 2015 the FDA announced that it had received drug adverse event reports of arthralgia, or severe pain in one or more joints. for the DPP-4 inhibitor class of diabetes medications.

We will continue to monitor the safety profile of Januvia, Onglyza, and the other DPP-4 diabetes drugs.

Recent Findings Come From The CARES Trial, A Postmarketing Safety Study Requested By FDA Back When Uloric Was Approved In 2009

At the recent American College of Cardiology (ACC) 2018 Annual Scientific Session meeting, the gout drug Uloric (febuxostat) was the subject of some safety concerns due to findings about a higher risk of death when compared to an alternative gout drug, allopurinol. However, the mechanism behind this difference was not readily apparent.

Allopurinol, approved by the FDA in 1966, and Uloric, approved in 2009, are two commonly prescribed medicines for gout. Takeda Pharmaceuticals is the drug company responsible for Uloric.

The findings presented at this 2018 ACC meeting came from the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Comorbidities (CARES) trial, or drug study, sponsored by Takeda Pharmaceuticals as an FDA postmarketing requirement.

At this point, there is no known explanation for the mortality risk seen with [Uloric (febuxostat)], William White, MD, of the University of Connecticut in Farmington, reported here at the American College of Cardiology meeting late-breaking clinical trial session....

Despite the unclear mechanism, the consistency of the finding across the intent-to-treat and on-treatment analysis made the excess mortality risk "relatively robust" such that it "likely should be used to inform policy," said Noel Bairey Merz, MD, of Cedars-Sinai Hospital in Los Angeles and a member of the discussion panel at the session.

In patients with gout and major cardiovascular coexisting conditions, [Uloric (febuxostat)] was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with [Uloric (febuxostat)] than with allopurinol.

One expects the FDA will be looking closely at these new CARES findings about all-cause and cardiovascular deaths associated with Uloric over the next several months.

Similarly, it is presumed that safety analyses by those medical researchers involved with the CARES trial are ongoing to evaluate the unexpected higher mortality rates in patients using Uloric in comparison to allopurinol.

Of course, we will be watching for significant developments regarding the safety profile of Uloric.

For this article we take a closer look at what had been discussed in the medical literature about the atherosclerosis side effect associated with Tasigna (nilotinib) no later than April 2013. We are doing this review because it was during April 2013 that Novartis Pharmaceuticals Canada Inc. took these actions:

Sent a so-called "Dear Doctor" letter in Canada (but not the US) warning about some serious side effects associated with Tasigna; and,

Issued a Tasigna drug label change in Canada (but not the US) with new information concerning those Tasigna side effects.

For that purpose, we have selected a Letter to the Editor published online April 22, 2013 by the medical journal Leukemia, which was written by Ayalew Tefferi, MD, of the Mayo Clinic's Division of Hematology within its Department of Medicine at Rochester, Minnesota.

Dr. Tefferi sets the stage, so to speak, by starting his Letter in this manner:

Atherosclerosis is the leading cause of death and morbidity in developed countries and is the culprit behind coronary artery disease (CAD), cerebral vascular disease (CVD) and peripheral artery occlusive disease (PAOD). Atherosclerosis leads to segmental narrowing and occlusion of arteries....

Thereafter, Dr. Tefferi begins his comments about the March 2013 article by TD Kim and several others:

In the second part of their study, Kim et al. reviewed 27 cases of TKI treatment-associated overt PAOD accrued from several collaborating centers and discovered that all but one of these patients were exposed to [Tasigna (nilotinib)] therapy, including 20 patients who were receiving [Tasigna (nilotinib)] as first- or second-line treatment of CP-CML. These events were severe enough to require percutaneous transluminal angioplasty in 33.3% of the cases, stent implantation in 22.2%, amputation in 22.2% and surgery in 18.5%. [Footnote omitted]

Next, Dr. Tefferi expands his scope of analysis to other medical journal reports about Tasigna and atherosclerosis-related diseases associated with this Novartis leukemia drug:

The observations from Kim et al. are consistent with those of earlier and more recent reports associating [Tasigna (nilotinib)] with accelerated atherosclerosis. Aichberger et al. reported a 33% incidence of PAOD, myocardial infarction, spinal infarction or subdural hematoma, among 24 CML patients treated with [Tasigna (nilotinib)]. Tefferi et al. described two patients who experienced sudden death or severe PAOD/CAD; continued [Tasigna (nilotinib)] treatment in the latter patient was associated with rapid progression of intra- and extracranial atherosclerosis leading to stroke. Most recently, Levato et al. reported their single-institution experience with 82 CML patients treated with imatinib (n=55) or [Tasigna (nilotinib)] (n=27); four (14.8%) [Tasigna (nilotinib)]-treated patients developed severe PAOD or other vascular disease. In contrast, none of the 55 imatinib-treated patients developed PAOD and only one experienced myocardial infarction, despite a longer median duration of treatment with imatinib (79.5 months) vs [Tasigna (nilotinib)] (21.5 months). [Footnotes omitted]

Taken together, the above observations strongly implicate [Tasigna (nilotinib)] therapy as being proatherogenic. Regardless of what the underlying mechanisms for this might be, the question is whether or not it is necessary or appropriate to subject newly diagnosed patients with CP-CML to this risk [of atherosclerosis associated with Tasigna (nilotinib)], considering the remarkable efficacy and safety of imatinib therapy.

In closing this article, I will point out that in the US there still has not been any "Dear Doctor" letter sent nor any Tasigna drug label change made by Novartis Pharmaceuticals Corporation regarding atherosclerosis, despite the actions taken by its Canadian counterpart during April 2013.

Less Warning About These Atherosclerosis-Related Diseases By Novartis In The US, It Seems, Compared To What Has Been Done By The Drug Company In Canada

Tasigna (nilotinib) was approved by the FDA in 2007 for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML).

In April 2013 a so-called "Dear Doctor" letter was sent out in Canada by the responsible drug company warning about some serious side effects associated with Tasigna and a drug label change with new information concerning those Tasigna side effects, or adverse events. Relevant parts of this April 9, 2013 letter from Novartis Pharmaceuticals Canada Inc. are set forth below:

Dear Healthcare Professional:

Subject: Updated information regarding the possible risk of developing atherosclerosis-related diseases with the use of TASIGNA* (nilotinib)

Novartis Pharmaceuticals Canada Inc. (“Novartis”), in collaboration with Health Canada, would like to inform you of important information regarding reports of atherosclerosis-related diseases in patients treated with TASIGNA* (nilotinib).

TASIGNA* belongs to the pharmacological class of protein-tyrosine kinase inhibitors....

Cases of atherosclerosis-related diseases have been reported during clinical trials and post marketing experience with the use of TASIGNA*.

Patients should be monitored for signs of atherosclerosis-related diseases during treatment with TASIGNA* Monitoring of lipid and glucose profiles should also be performed before and frequently during treatment with TASIGNA* and as clinically indicated.

Updated information regarding Tasigna safety profile has been added to the product monograph under the Warnings and Precautions, common clinical adverse drug reactions and post-marketing adverse reactions sections.

In a Phase III study (A2303) in newly diagnosed Ph+ CML patients, atherosclerosis-related diseases such as peripheral arterial occlusive disease, femoral artery stenosis, coronary artery stenosis, carotid artery stenosis, and cerebrovascular accident were reported in patients taking TASIGNA* (5.0% for TASIGNA* 300 mg BID and 6.1% for TASIGNA* 400 mg BID). A review of the Novartis global safety database search (between January 1st, 2005 and January 31, 2013) identified a total of 277 cases of atherosclerosis, of which 14 were Canadian cases. The cumulative patient exposure since the first launch of TASIGNA* in 2007 is estimated to be approximately 39,299 patient-years....

*TASIGNA is a registered trademark.

We point out that there was no similar "Dear Doctor" letter sent in the US by Novartis Pharmaceuticals Corporation in 2013, nor was any similar Tasigna drug label change made by Novartis in the US back then.

Several recent studies have reported vascular toxicity with [Tasigna (nilotinib)] (Table 1). In a retrospective multicenter analysis of 179 patients, 11 patients (6.2%) developed peripheral arterial disease (PAD) involving lower limbs. Most striking was the severity of PAD; eight patients required invasive therapy (angioplasty and stent placement), and four patients required amputation. A single-center study of 24 patients reported PAD in three patients, all requiring angioplasty or surgery. A number of other retrospective studies from single institutions have confirmed a higher than expected incidence of peripheral or cardiac ischemic events in patients treated with [Tasigna (nilotinib)] (Table 1). The finding that cardiovascular risk factors were common in patients with vascular [adverse events (AEs)], combined with the elevations in glucose and cholesterol, suggested that [Tasigna (nilotinib)] may aggravate a pre-existing arteriosclerotic condition. In a meta-analysis of the [International Randomized Interferon Versus STI571 (IRIS)], Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS), and [Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd)] studies, peripheral arterial occlusive disease (PAOD) was reported in seven (1.3%) of 556 patients treated with [Tasigna (nilotinib)], three (0.6%) of 533 patients treated with no [tyrosine kinase inhibitor (TKI)], and two (0.2%) of 1,301 patients treated with imatinib. A 3-year follow-up of the ENESTnd trial suggests a higher incidence of vascular events in patients treated with [Tasigna (nilotinib)] compared with imatinib; eight (1.4%) of 556 and 11 (2.0%) of 556 [Tasigna (nilotinib)]-treated patients had PAOD and ischemic heart disease, respectively, whereas these occurred in none (0%) and one (0.4%) of 280 patients in the imatinib group, respectively. These data are more striking at 6-year follow-up. Twenty-eight (10%) of 279 patients treated with [Tasigna (nilotinib)] 300 mg twice per day, 44 (15.9%) of 277 patients treated with [Tasigna (nilotinib)] 400 mg twice per day, and seven (2.5%) of 280 patients treated with imatinib 400 once per day had cardiovascular events. Cardiovascular events included ischemic heart disease, ischemic cerebrovascular disease, and peripheral artery disease, suggesting that the [Tasigna (nilotinib)]-associated toxicity occurs in all arterial beds. Few venous events were seen in each arm. Importantly, the dose-dependent increased risk of events in the [Tasigna (nilotinib)] arms implicates a drug-dependent process. [Footnotes omitted.]

To break down that dense paragraph a bit, here is a list of the four serious side effects, or adverse events, linked to Tasigna by this 2015 medical journal article:

peripheral arterial disease (PAD) involving lower limbs;

peripheral arterial occlusive disease (PAOD);

ischemic heart disease; and

ischemic cerebrovascular disease.

To date there has still not been any "Dear Doctor" letter sent in the US by Novartis about these four Tasigna side effects.

In the "WARNINGS AND PRECAUTIONS" part of the Tasigna drug label, there is this information:

5.4 Cardiac and Arterial Vascular Occlusive Events

Cardiovascular events, including arterial vascular occlusive events, were reported in a randomized, clinical trial in newly diagnosed CML patients and observed in the postmarketing reports of patients receiving nilotinib therapy. With a median time on therapy of 60 months in the clinical trial, cardiovascular events, including arterial vascular occlusive events, occurred in 9.3% and 15.2% of patients in the Tasigna 300 and 400 mg twice daily arms, respectively, and in 3.2% in the imatinib arm. These included cases of cardiovascular events including ischemic heart disease-related cardiac events (5.0% and 9.4% in the Tasigna 300 mg and 400 mg twice daily arms respectively, and 2.5% in the imatinib arm), peripheral arterial occlusive disease (3.6% and 2.9% in the Tasigna 300 mg and 400 mg twice daily arms respectively, and 0% in the imatinib arm), and ischemic cerebrovascular events (1.4% and 3.2% in the Tasigna 300 mg and 400 mg twice daily arms respectively, and 0.7% in the imatinib arm). If acute signs or symptoms of cardiovascular events occur, advise patients to seek immediate medical attention. The cardiovascular status of patients should be evaluated and cardiovascular risk factors should be monitored and actively.

And in the "PATIENT COUNSELING INFORMATION", there is some additional guidance for doctors who are prescribing Tasigna:

Going back to the Tasigna situation in Canada, the current Product Monograph for TASIGNA® [PDF download file] (accessed 2/26/18) warns about these particular side effects (and some others, also) in the WARNINGS AND PRECAUTIONS section. And that warning is highlighted, if seems, by placing the following text within a box captioned "Serious Warnings and Precautions":

Why the different treatment of this Tasigna drug safety issue by Novartis in Canada, i.e., apparent stronger warnings, as opposed to in the US?

For whatever reason, it seems Novartis has issued stronger warnings about the ischemic heart disease, ischemic cerebrovascular events, and peripheral arterial occlusive disease side effects associated with Tasigna in Canada compared with what the drug company has done, or not done, in the US.

If you have some insight about this divergent Tasigna warnings situation, please share it by leaving a Comment below.

Current Number Of Drug Injury Lawsuits Filed In Each Of These Ongoing Federal Court MDL Cases: February 2018 JPML Report

At the present time there are four federal court Multidistrict Litigation (MDL) cases for drug injury lawsuits concerning several different types of diabetes medicines with unique sets of side effects.

We supplement that information provided by the JPML with the primary side effects that are the subject of personal injury lawsuits and wrongful death lawsuits filed in each of these diabetes drug MDL cases.

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